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Persistence of Sexual Dysfunction Side Effects after Discontinuation of Antidepressant Medications: Emerging Evidence



Post-market prevalence studies have found that Selective Serotonin Reuptake Inhibitor (SSRI) and Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) sexual side effects occur at dramatically higher rates than initially reported in pre-market trials. Prescribing and practice conventions rest on the untested assumption that individuals who develop sex-ual dysfunction secondary to SSRI and SNRI antidepressant medications return fully to their pre-medication sexual func-tioning baseline shortly after discontinuing treatment. Most individuals probably do return to their previous level of sexual functioning, however recent case reports, consumer-provided Internet-based information, incidental research findings, and empirical evidence of persistent post SSRI sexual benefits in the premature ejaculation literature suggest that for some in-dividuals, SSRI and SNRI-emergent sexual side effects persist indefinitely after discontinuing the medications. The litera-ture poorly captures the full spectrum of SSRI/SNRI sexual side effects, and a lack of systematic follow-up in the sexual side effects research precludes detection of post SSRI/SNRI sexual dysfunction, leaving the formal knowledge base in-adequate and even inaccurate, raising informed consent issues, and leaving clinicians vulnerable to practicing in ways that may be hurtful to patients in spite of their best efforts to inform themselves.
42 The Open Psychology Journal, 2008, 1, 42-50
1874-3501/08 2008 Bentham Open
Open Access
Persistence of Sexual Dysfunction Side Effects after Discontinuation of
Antidepressant Medications: Emerging Evidence
Audrey S. Bahrick*
University Counseling Service, 3223 Westlawn S., The University of Iowa, Iowa City, Iowa 52242-1100, USA
Abstract: Post-market prevalence studies have found that Selective Serotonin Reuptake Inhibitor (SSRI) and Serotonin-
Norepinephrine Reuptake Inhibitor (SNRI) sexual side effects o ccur at dramatically higher rates than initially reported in
pre-market trials. Prescribing and practice conventions rest on the untested assumption that individuals who develop sex-
ual dysfunction secondary to SSRI and SNRI antidepressant medications return fully to their pre-medication sexual func-
tioning baseline shortly after discontinuing treatment. Most individuals probably do return to their previous level of sexual
functioning, however recent case reports, consumer-provided Internet-based information, incidental research findings, and
empirical evidence of persistent post SSRI sexual benefits in the premature ejaculation literature suggest that for some in-
dividuals, SSRI and SNRI-emergent sexual side effects p ersist indefinitely after discontinuing the medications. The litera-
ture poorly captures the full spectrum of SSRI/SNR I sexual side effects, and a lack of systematic follow-up in the sexual
side effects research precludes detection of post SSRI/SNRI sexual dysfunction, leaving the formal knowledge base in-
adequate and even inaccurate, raising informed consent issues, and leaving clinicians vulnerable to practicing in ways that
may be hurtful to patients in spite of their best efforts to inform themselves.
Key Words: SSRI, iatrogenesis, persistent sexual side effects, sexual dysfunction, genital anesthesia.
The present article discusses issues and evidence related
to sexual side effects of selective serotonin reuptake inhibi-
tors (SSRIs) including fluoxetine (Prozac), paroxetine
(Paxil), sertraline (Zoloft), citalopram (Celexa), escitalopram
(Lexapro), and fluvoxamine (Luvox), and the serotonin-
norepinephrine reuptake inhibitor (SNRI) venlafaxine (Ef-
fexor)1. Sexual side effects are known to occur as a result of
drug treatment, but their prevalence is underestimated in the
product literature, and the research literature poorly captures
the quality and scope of the sexual side effects and how dis-
tressing they may be to patients.
The SSRIs and SNRIs are approved and considered first
line treatments for depressive disorders, generalized anxiety
disorder, panic disorder, social phobia, obsessive-compulsive
disorder, bulimia, premenstrual dysphoric disorder, and post
traumatic stress disorder. Increasingly, they are prescribed
off-label [1] to treat conditions such as peri-menopausal and
post-menopausal hot flashes, chronic fatigue syndrome,
chronic pain syndromes, premature ejaculation, and paraphil-
ias. In the latter two conditions, the sexual side effects are
intended as the primary and desired effects.
Recent estimates are that on average, 43% of patients
seen by psychologists take medication adjunctively to psy-
chotherapy [2], and that one in eight adult American has
*Address correspondence to this author at the University Counseling Serv-
ice, 3223 Westlawn S., The University of Iowa, Iowa City, Iowa 52242-
1100, USA; Tel: 319 335-7294; Fax: 319 335-7298;
1 Sexual side effects of the SNRI du loxetine (Cymbalta) are less well-studied.
taken an SSRI or SNRI over the last ten years [3]. In the pre-
sent author’s practice setting at a large university counseling
service, nearly fifty percent of the generally high-functioning
and sexually active or sexually motivated young adult clien-
tele are taking psychotropic medications, usually SSRIs or
SNRIs [M. Harris, Clinical Director, University of Iowa
Counseling Service personal communication, Dec.5, 2007].
There is a growing consensus that psychologists need to be
knowledgeable about psychotropic medication effects and
side effects as a competency issue and a standard of care [4].
Given mental health professionals’ responsibility for client
welfare, when clients are taking or are contemplating taking
SSRIs/SNRIs, psychologists have an obligation to inform
clients of the possibility of sexual side effects, and in col-
laboration with clients and prescribing professionals, to con-
sider the impact of adding a new, medication-related sexual
dysfunction to the client’s condition. Prescribing psycholo-
gists are optimally positioned to monitor and to be respon-
sive to treatment implications of emergent medication side
effects [5] .
The possibility that treatment-related sexual side effects
may persist in some patients after stopping the medications
seems to be unrecognized among the research and profes-
sional communities, yet is increasingly identified among
Internet communities [e.g.;], and described
in a series of recent case reports [6-9]. My immersion in the
formal literature, in my clinical practice, and in consumer-
based Internet information has led me to believe that the ex-
isting knowledge base with regards to SSRI/SNRI sexual
side effects is unintegrated, inadequate, and even inaccurate,
raising concerns about informed consent, and leaving clini-
Persistence of Sexual Dysfunction Side Effects The Open Psychology Journal, 2008, Volume 1 43
cians vulnerable to unknowingly contributing to iatrogenic
The present article presents available evidence indicating
that SSRI and SNRI-emergent sexual dysfunctions, for an
unknown number of patients, may not resolve upon cessation
of medication. As discussed in Rivas-Vasquez, Rey, Blais, et
al. [5], sorting out the etiology of sexual dysfunction can be
challenging. Evidence considered in the present article is
confined to sexual dysfunctions that were not present at
baseline, and emerged only with drug initiation, maximizing
the probability that the dysfunction is drug-induced. Evi-
dence presented comes from a variety of sources including
incidental research findings, empirical findings, case reports,
and consumer-reported experiences. In addition, two distinc-
tive sexual symptoms are highlighted that are rarely reported
in the research literature, but are often identified as among
those symptoms that persist after treatment discontinuation
in both case reports and among members of an Internet
community. It is proposed that these unusual symptoms,
genital anesthesia and anhedonic orgasm/ejaculatory anhe-
donia (i.e. diminished or absent genital- tactile sensitivity
and orgasm or ejaculation that is not associated with physical
sensations of pleasure), often missed by our assessment in-
struments, may serve as lingering markers of past SSRI or
SNRI exposure [10], further helping to distinguish medica-
tion effects from sexual dysfunctions that may be primarily
of psychological origin.
Searching the data bases of research studies yielded no
published investigations that bear directly on the problem of
persistent sexual side effects after discontinuation of SSRIs/
SNRIs. With few exceptions, the research investigating
SSRI/SNRI sexual side effects has not included follow up
after discontinuation of the medication. However a number
of investigations, not primarily motivated by concern about
long term drug safety, have followed SSRI-emergent sexual
side effects for a six month period after discontinuation of
the medications [11-13]. The researchers did not interpret
their findings as raising concerns about the persistence of
sexual side effects after discontinuation of SSRIs, but such
alternative interpretations of the findings will be discussed.
Post market research has clearly established that the
SSRIs and SNRIs can affect most every aspect of sexual
functioning at rates significantly higher than the 2-16% rates
reported in pre-market trials and currently listed in the drug
insert literature. Large prospective studies in which baseline
assessment excludes participants with pre-existing sexual
dysfunction have found rates of treatment-emergent sexual
dysfunctions such as decreased libido, delayed orgasm, anor-
gasmia, erectile dysfunction, and difficulties with arousal, of
between 36 and 70% [14, 15]. The 2-16% pre-market rates
of SSRI and SNRI-induced sexual side effects are based on
spontaneous reports of individuals in initial trials who had
been on the medications a short time. When individuals are
directly and systematically asked about changes in sexual
functioning via a structured clinical interview or a self-report
inventory, dramatically higher rate information is obtained as
compared with reliance on individuals to spontaneously
als to spontaneously volunteer personally sensitive informa-
tion about changes in sexual functioning [15, 16].
Current American Psychiatric Association treatment
guidelines do not recognize clinically significant differences
in efficacy among the various medications [17]. The choice
to prescribe one SSRI or SNRI over another is often based
on the known side effect profile, with the reported impact on
sexual functioning often a deciding factor [18]. While sexual
side effects are probably the most-researched of all the SSRI
and SNRI side effects, the foci, motivated by competing
drug companies’ efforts to gain a market share, have been
heavily on: determining the comparative prevalence rates of
a variety of sexual side effects; determining strategies for
managing the sexual side effects: demonstrating the efficacy
of one medication to serve as an antidote to the sexual dys-
function caused by another; and also on the ejaculation-
delaying benefits of the various SSRIs when used as an off-
label treatment for premature ejaculation (i.e. see Waldinger
[19] for a review).
Despite the substantial body of literature devoted to
comparative sexual side effects prevalence rates and anti-
dotes, there is little indication of clinically significant differ-
ences among the medications with regards to rates of associ-
ated sexual side effects [20] and no strategy or antidote has
proven reliably effective for alleviating the SSRI or SNRI-
induced sexual side effects. While the consistent impression
given by the literature is that sexual side effects may be eas-
ily resolvable in consultation with the prescriber, the man-
agement of antidepressant sexual side effects, according to
Balon [16], should currently be seen as an art and not a sci-
ence. An estimated 5 to 10% of individuals may experience a
diminution of the SSRI or SNRI emergent sexual side effects
over time as they remain on the medication [21], but for the
vast majority, the sexual side effects are intractable and will
continue for at least as long as they take the medication [14,
The research questions related to SSRI/SNRI sexual side
effects that are of most interest to industry sponsors are not
the same questions that are of most interest and urgency
from a public health perspective. As a result, important gaps
in knowledge remain. These gaps include, but are not limited
to: 1) Information as to which sexual side effects are most
characteristic of the SSRIs/SNRIs; 2) The degree to which
side effects remain stable or change over the course of longer
term treatment; 3) When and whether individuals who de-
velop sexual side effects secondary to the medications return
fully to their pre-medication sexual functioning baseline; 4)
What impact the medications may have on fertility and re-
productive health, and; 5) In what ways the medications may
affect the developing sexuality of adolescents and children.
Gaps 1, 2, and 3 will be explored more fully in this article.
While the potential impacts of SSRIs and SNRIs on fer-
tility and reproductive health, and on adolescents’ develop-
ing sexuality are beyond the scope of this article, there are
reasons to be concerned: Tanrikut and Schlegel [22] recently
found SSRI usage in two men to be related to impaired se-
men parameters, which apparently improved when the men
discontinued the medications. And Scharko [23] notes that
while sexual side effects may be expected to occur in adoles-
cents at rates similar to those found in adults, his review of
the adolescent SSRI literature found a nearly complete lack
44 The Open Psychology Journal, 2008, Volume 1 Audrey S. Bahrick
of information or research related to SSRI sexual side effects
in adolescents, and no developmentally appropriate instru-
ments for assessing the medications’ impact on adolescent
sexual functioning.
The assumption of a sexual-functioning return to baseline
shortly after cessation of the medications is deeply embed-
ded in the literature, as well as in the conventional approach
to practice and prescribing [10]. Yet no primary source was
found to substantiate the resolution of sexual side effects: no
study was found that systematically and intentionally fol-
lowed the course of SSRI or SNRI-induced sexual dysfunc-
tion after discontinuation of the medications for the drug-
safety-related purpose of determining when and to what de-
gree the sexual side effects resolve. A search of the literature
resulted in identifying only a single study in which fluoxet-
ine-emergent sexual side effects were reported to have re-
solved within one to three weeks of cessation of medication
[24]. The author does not specify when or by what means the
follow-up information was obtained or how many of 54 pa-
tients in this two-year, naturalistic, private-practice based
study had discontinued the medication and were available for
follow up. Treatment-emergent sexual side effects probably
do resolve for most individuals after discontinuing the medi-
cations, yet since sexual side effects might persist after treat-
ment cessation for some individuals, researchers have an
obligation to design studies so as to assess this likelihood. In
the vast majority of studies of SSRI sexual side effects, no
post-treatment follow-up is included in the research protocol,
and/or participants are still actively taking the medication at
study endpoints.
The SSRI/SNRI sexual side effects literature generally
reflects the perspective that the sexual side effects pose a
threat to treatment compliance [i.e. 30, 37, 43]. Indeed, it is
believed that up to two-thirds of patients discontinue a
guidelines-recommended course of antidepressants due to
adverse events, particularly sexual dysfunction [25]. Less
frequently mentioned, or only perfunctorily treated is the
responsibility of prescribing professionals to address the
interaction of a new or worsening sexual dysfunction with
the condition being treated, and the impact on general quality
of life in the collaborative negotiation of treatment alterna-
tives. The failure of the SSRI-research literature to fully en-
gage in addressing the psychological costs of medication-
induced sexual dysfunction suggests that clinicians may
sometimes fail to invite fully collaborative interactions in
response to patients’ concern about SSRI-emergent sexual
dysfunctions. Instead, they may engage in something more
akin to what Higgens et al. [26] describe as a “compliance
monologue”[p. 441] motivated by, among other things, the
professional’s own discomfort with initiating an in-depth
conversation about sexual functioning, bolstered by an a
priori allegiance to a pharmacological model of treatment.
In response to individuals who express concern about
treatment-emergent sexual side effects, clinicians are advised
to reassure patients that the side effects are “medically be-
nign” [27 p. 23] and that “ all data suggest return of sexual
functioning to baseline once the medication is stopped” [28
p. 106]. The conventional wisdom seems to dismiss even the
possibility that sexual side effects may continue after stop-
ping the medications by defining true drug-induced sexual
dysfunction as, “that which occurs after the agent is started
or the dosage is increased, is not partner-specific, is not life-
long or recurrent, and resolves when drug therapy is discon-
tinued (italics added) [29, p. 825]; or, that which “ is not
better explained by physical illness or stress, whose onset is
with drug initiation or dose increase, is present in all sexual
situations, reappears with reintroduction of the drug, and
dissipates with drug discontinuation or dose reduction” (ital-
ics added) [30, p. 1489].
The assumption of benignness, along with such intui-
tively attractive, yet empirically untested definitions of drug-
induced sexual side effects, contributes to the systematic
failure to include post-treatment follow-up in our research
designs. These assumptions also underscore the reasons that
clinicians, and even patients themselves may fail to consider
past SSRI or SNRI medication use as a possible cause for
otherwise unexplained persistent sexual dysfunctions. Cur-
rent definitions are unsatisfactory, as they do not allow for
the possibility that sexual side effects that begin on medica-
tion and persist after medication discontinuation could be
There are indications that some SSRI/SNRI sexual side
effects thought to be rare are actually common [10]. The
most frequently documented sexual side effects are dimin-
ished libido, unspecified problems with arousal, and delayed
orgasm or anorgasmia. Delayed ejaculation or orgasm, and
anorgasmia have been those symptoms that the literature
links most clearly and most frequently to SSRI treatment, vs.
to depression itself [16]. However the symptoms of genital
anesthesia and pleasureless orgasm, outside the range of
common experience and appearing to often occur together,
are frequently reported among men and women in Internet
communities, in an accumulating case reports literature [6-9,
31-36], and in one research investigation [37].
These counterintuitive symptoms can be described as a
preservation of aspects of normal physical sexual function-
ing, but with a loss of the concurrent capacity to experience
sexual pleasure or arousal. Genital anesthesia has been de-
scribed in Internet forums and in case reports as genitals that
are numb or nearly numb, which may respond to stimulation
by erection or lubrication, but without attendant subjective
feelings of arousal. Pleasureless orgasm or ejaculatory anhe-
donia can be described as orgasm or ejaculation that is pre-
ceded by little sense of building arousal, is identifiable by
rhythmic perineal muscle contractions in women or by ejacu-
lation in men, but is experienced as pleasureless or nearly so.
These qualitatively different symptoms are not easily classi-
fiable in regard to any specific category of the sexual re-
sponse cycle, and as Bahrick has noted, elude capture in
most prevalence studies [10]. Decreased orgasmic intensity
or ejaculatory anhedonia are not mentioned in recent reviews
of disorders of ejaculation and orgasm in men [38], or in
women [39], and SSRI/SNRI-related decreased genital sensi-
tivity or genital anesthesia, when mentioned, are reported to
be uncommon [6, 14, 15]. However it is more accurate to say
that the symptoms are uncommonly assessed.
Michael and Mayer [32] describe a case of fluoxetine-
induced anesthesia of the vagina and nipples in an initially
Persistence of Sexual Dysfunction Side Effects The Open Psychology Journal, 2008, Volume 1 45
depressed woman who had experienced lowered libido con-
currently with depression. Michael and Mayor linked her
genital and nipple anesthesia to the treatment and not to the
patient’s condition, as the anesthesia persisted even when the
initially depressed patient became euthymic. Deisenhammer
and Trawoger [36] demonstrated with a re-challenge test that
genital anesthesia was indeed caused by treatment with cita-
lopram in the case of a 36 year old man treated with citalo-
pram for an adjustment disorder with depressed mood. The
man, reported not to have any preexisting sexual dysfunc-
tions, experienced penile anesthesia after three days on the
medication. The symptom resolved shortly after stopping the
medication, which he’d continued for three weeks due to its
mood lifting effect. A year later, the man, described as
healthy and with no mood or sexual difficulties, consented to
re-exposure to citalopram. He again experienced penile anes-
thesia after several days on citalopram, which again resolved
several days after stopping the medication.
Deisenhammer and Trawoger [36] state that genital anes-
thesia is probably associated with all antidepressants that
enhance serotonergic neurotransmission. Clayton and Mon-
tejo [21] point to a possible basis for the symptom, noting
that serotonergic medications may decrease genital sensation
via diminished nitric oxide function. Nitric oxide is integral
to penile and clitoral tumescence. Deisenhammer and Tra-
woger [36] call for controlled studies to evaluate the inci-
dence of SSRI induced genital anesthesia. To the present
author’s knowledge, no such controlled studies have been
performed. Indeed, our literature supports the assumption
that genital anesthesia and ejaculatory anhedonia/pleasure-
less orgasm are rare by failing to systematically include the
symptoms in our instruments, and by failing to report them
transparently when they are included [10].
According to Clayton and Montejo [21], The Changes in
Sexual Functioning Questionnaire (CSFQ) [40], and the Ari-
zona Sexual Experiences Scale (ASEX) [41], are the primary
validated instruments used to assess sexual dysfunction sec-
ondary to psychotropic medication. Neither the CSFQ nor
the ASEX include specific queries related to changes in
genital sensitivity. And neither unambiguously captures
pleasureless orgasm or ejaculatory anhedonia; the CSFQ
fails to do so by scoring decreased orgasmic intensity to-
gether with items assessing timing and frequency of orgasm,
and the ASEX because the inquiry regarding changes in sat-
isfaction from orgasm is less specific than changes in inten-
sity of orgasm.
To the present author’s knowledge, the Rush Sexual In-
ventory is the only instrument, validated in 2005 [42], for
assessing medication-related sexual changes that includes
specific queries related to both changes in sensitivity of ex-
ternal genitalia as well as changes in orgasm intensity. How-
ever, as items are answered in a yes/no format, the instru-
ment captures the presence, but not the severity of the symp-
toms. Two studies were found that assessed SSRI-related
sexual side effects using the Rush Sexual Inventory:
Ferguson [43] did not report specific symptom results, and
Zajecka et al. [37] reported only partial results. Zajecka et al.
[37] found that among 42 depressed patients taking a variety
of SSRIs, 28% of women reported treatment-emergent de-
creased genital sensitivity and 25% of men reported treat-
ment-emergent decreased intensity of orgasm, suggesting the
symptoms are not uncommon. While data were collected for
both genders for both symptoms, results were reported for
only one of the symptoms for each gender. The article’s ab-
stract notes the Rush Sexual Inventory’s utility for follow-up
assessment, however no follow-up data were provided re-
garding the resolution of the SSRI-induced sexual side ef-
Genital anesthesia and pleasureless orgasm or ejaculatory
anhedonia should be of special interest to both researchers
and clinicians. The symptoms are unknown in the general
population, are not known to be associated with any condi-
tions or disorders for which SSRIs or SNRIs are prescribed,
yet seem to be distinctive markers of medication treatment.
When treatment-emergent sexual side effects persist after
discontinuing SSRIs or SNRIs, patients’ reports may be dis-
counted, disbelieved, ascribed to a relapse of the preventing
problem, or to the emergence of yet a new mental health
problem by professionals to whom individuals turn for help.
Thus, Bahrick has suggested that among all the sexual side
effects that may emerge during treatment or persist after ces-
sation, genital anesthesia and ejaculatory anhedonia may
provide the most compelling links to the treatment rather
than the conditions being treated [10].
An Incidental Finding
Montejo et al. [11] appear to have found incidental evi-
dence of SSRI-induced sexual side effects continuing after
cessation of the medication. The study’s aim was to assess
the impact of changing to another medication in patients
whose depressive symptoms had successfully remitted with a
variety of SSRIs, but who had developed treatment-emergent
sexual dysfunction. Patients were switched either to amin-
eptine (n=47), an atypical tricyclic antidepressant that is no
longer available, or to paroxetine (n=38). A third group of
depressed patients was treated with amineptine only (n=26)
and had no prior SSRI treatment. All three groups were fol-
lowed with multiple assessments over a six month period.
Montejo et al. [11] report for those patients taking amin-
eptine only, amineptine was not a cause of secondary sexual
dysfunction, and also effectively treated depressive symp-
toms. In the group switched to amineptine, the incidence of
sexual dysfunction dropped from 100% to 55% over the six
month period, while depressive symptoms remained in re-
mission. In the group switched to paroxetine, sexual dys-
function decreased only slightly from 100% to 89.7% after
six months. The authors interpret these findings to support
with high confidence (p<.001) the conclusion that amin-
eptine is an effective antidepressant that is able to signifi-
cantly improve the SSRI-caused sexual dysfunction, yet
maintain the efficacy of the antidepressant treatment used
before. An alternative interpretation is that for 55% of indi-
viduals switched to a medication that successfully treated
depressive symptoms and was not a cause of secondary sex-
ual dysfunction, the initial SSRI-induced sexual dysfunction
persisted for at least six months after discontinuing the SSRI
46 The Open Psychology Journal, 2008, Volume 1 Audrey S. Bahrick
Empirical Evidence: Persistent Sexual Benefits after Dis-
continuation of SSRIs
The well-established ejaculation-delaying effects of all of
the SSRIs has led to their ubiquitous off-label use as a treat-
ment for premature ejaculation (PE), and motivated industry
to seek approval of SSRIs for a new indication reported to
affect approximately 30% of men globally across all age
groups [44] and to affect up to 70% of men at some point in
their sexual lives [45]. The large emerging literature related
to SSRIs as a treatment for PE asks which SSRIs may have
the longest or most potent ejaculation-delaying effect;
whether chronic or on demand administration of SSRIs is
preferable and in what dose, whether newer shorter-acting
SSRIs may prove more efficacious than those already on the
market, and whether the medications may provide lasting
benefits beyond treatment discontinuation. With current in-
the-field practice moving well ahead of demonstrated long-
term safety, a recent survey of urologists indicated SSRI
treatment is the most common first-line approach to manag-
ing premature ejaculation [46].
Two recent studies found robust evidence for sustained
post-treatment effects of SSRIs on ejaculation latency [12,
13]. Safarinejad and Hosseini [12] evaluated citalopram as a
treatment for PE in a prospective, double-blind, placebo con-
trolled, fixed dose (20 mg.), randomized study of fifty-eight
non-depressed, psychologically and physically healthy men
whose only sexual complaint was PE. Premature ejaculation
was defined as intravaginal ejaculatory latency time (IVELT)
of less than two minutes in more than 90% of coitus. The
impact on sexual functioning of the citalopram (n=29) and
placebo (n=29) treatments was assessed every two weeks
during the twelve-week treatment period, and in three and
six month follow-ups after cessation of treatment. Safety and
efficacy measures included: changes in IVELT which sub-
jects recorded with a stop watch; frequency of intercourse,
adverse drug events which subjects recorded in an apparently
open format diary, and the use of a subset of six out of fif-
teen questions from the International Index of Erectile Func-
tion (IIEF) reflecting a domain of “intercourse satisfaction”.
The authors report significantly improved ejaculation
latency (IVELT) scores (p<.001) for the citalopram group vs.
the placebo group beginning at week one and continuing
throughout the 12-week treatment phase, and improved in-
tercourse frequency as well as satisfaction in the citalopram
group over the placebo group (p<0.05) by week 12. They
report no adverse treatment-related changes in erectile func-
tion for the treatment group, or any negative impacts on any
aspect of sexual functioning. And, astonishingly, Safarinejad
and Hosseini found the significant ejaculation delaying bene-
fits in the citalopram group to be robustly sustained (p<.001)
after discontinuing the medication in both the three and six
month follow-up assessments. The authors offer a biologi-
cally-based hypothesis regarding the ejaculation delaying
benefits of citalopram, and conclude that “the real, long term
efficiency of citalopram was proved after treatment cessa-
tion” [12 p.169].
Arafa and Shamloul [13] evaluated sertraline, (50 mg.),
as a treatment for PE in a large, prospective, single-blind,
placebo-controlled, crossover study of 147 healthy men.
Premature ejaculation was defined as ejaculation that oc-
curred within two minutes of vaginal intromission. Included
in the study were men who met criteria for PE on a validated
instrument, the Arabic Index of Premature Ejaculation
(AIPE), and excluded were men with erectile dysfunction,
low sexual desire, inhibited orgasm, psychiatric or physical
illness. Patients were divided into two groups: group 1
(n=77) received sertraline daily for four weeks, while group
2 (n=70) received placebo for four weeks. After a four week
washout phase, group 1 received four weeks of placebo and
group 2 received four weeks of sertraline. Intravaginal ejacu-
latory latency time (IVELT) was measured with a stopwatch
by the men’s partners. Frequency of coitus and IVELT were
compared for both groups, and men completed the AIPE at
the end of each treatment phase, and monthly during a six
month follow-up phase.
Of the original 147 participants, 81% achieved an in-
crease in ejaculatory latency over pretreatment levels with
the sertraline treatment. (p<.001). The authors note that no
participants reported erectile dysfunction, reduced libido or
reduced intensity of orgasm. Of 126 men who achieved in-
creased ejaculation latency during sertraline treatment, one
hundred were followed for a period of six months after medi-
cation discontinuation.
The follow up consisted of once monthly visits during
which participants completed the AIPE. Arafa and Shamloul
[13] report that of these, 66 experienced relapse of PE within
the six month period, evidenced by low AIPE scores. The
other 34 men’s AIPE scores indicated maintenance of the
benefit of ejaculatory delay. Arafa and Shamloul note that
the sustained effect of SSRI drugs on ejaculation latency
after drug withdrawal is not widely known. They conclude
that the present study confirms the usefulness of sertraline in
delaying ejaculation, and call for further large cohort studies
to evaluate sertraline’s sustained effects on ejaculation la-
tency, specifically after drug discontinuation” [p.537].
The Safarinejad & Hosseini [12] and Arafa & Shamloul
[13] data support the efficacy of SSRIs to delay ejaculation,
but are inadequate to establish safety, despite Safarinejad &
Hosseini’s conclusion that citalopram is “safe and effective”
(p. 169) when administered as a chronic, daily, long-term
treatment for PE. Given the pervasiveness [18] and random-
ness [47] with which SSRIs may affect any phase of the sex-
ual response cycle [48] the literature would lead us to expect
ejaculation delay to have been accompanied at least in some
instances by other unwanted sexual side effects. For exam-
ple, in a prospective study of SSRI sexual side effects in in-
dividuals taking the medications for a variety of approved
reasons who had no sexual dysfunctions at baseline, Montejo
et al. [14] found citalopram or sertraline-treated patients re-
ported, respectively, 62.1% and 54.7% treatment-emergent
decreased desire; 63.3% and 56.6% delayed orgasm or ejacu-
lation; and 34.8% and 28.9% erectile dysfunction or de-
creased vaginal lubrication.
Aspects of the design of the Safarinejad and Hosseini
[12] study may have contributed to the absence of findings
of concurrent unwanted sexual side effects. Safarinejad and
Hosseini note that their assessment instrument, the Interna-
tional Index of Erectile Function (IIEF) is a 15-item, cross-
culturally validated, psychometrically sound and sensitive
instrument for detecting treatment-related changes in erectile
Persistence of Sexual Dysfunction Side Effects The Open Psychology Journal, 2008, Volume 1 47
functioning. The authors used the whole of the 15-item IIEF
only at their baseline assessment to screen out men with ex-
isting erectile dysfunction. For their assessment of treatment
and post-treatment changes, the authors elected to use a sub-
set of six out of the total fifteen IIEF items, comprising a
domain of “intercourse satisfaction”. Excluded in the ongo-
ing treatment and post treatment assessments were all items
concerning erectile functioning. Apparently, participants
were expected to self-identify erectile dysfunction, or other
sexual adverse events using a diary given to them for record-
ing adverse events. Systematic use of the entire 15 items of
the validated instrument for all assessments would have pro-
vided a more sensitive method for detecting changes in erec-
tile functioning.
Arafa and Shamloul [13] note that the AIPE is a vali-
dated instrument that reliably identifies men with PE and
includes assessment of sexual desire, erectile functioning,
ejaculation latency, ejaculation control, patient satisfaction,
perceived partner satisfaction, and anxiety-depression status
related to sexual intercourse. The authors separately present
results for each of the seven questions of the AIPE pertaining
to the active treatment phase. While the authors note that
post-treatment follow-up consisted of monthly administra-
tion of the AIPE, results presented are in the form of qualita-
tive comments indicating that AIPE scores were “high” in
the group of 34 men who maintained benefits after six
months, and “low” in the group of 66 men who relapsed after
six months. Changes on the seven domains of sexual func-
tioning as assessed by the AIPE after treatment discontinua-
tion are not presented or discussed. As the study excluded
men with sexual problems other than PE, it is of interest to
determine whether any participants reported new or different
sexual problems post-treatment. The authors note that during
active treatment, no erectile dysfunction, reduced libido, or
reduced orgasmic intensity were reported. As “reduced in-
tensity of orgasm” is not included among the seven queries
in the AIPE, it is not clear how this information was obtained
or how systematically.
The results of the Safarinejad and Hosseini [12] and
Arafa and Shamloul [13] studies suggest a need for research
to clarify the reasons for the persistent sexual benefits after
stopping citalopram and sertraline. The placebo and cross-
over designs establish that the ejaculation delay during active
treatment is a medication effect. While a reduction in per-
formance anxiety may potentially contribute to sustained
ejaculatory control after cessation of medication [49], Arafa
and Shamloul do not present or discuss post-treatment values
for the AIEF item related to “anxiety-depression status with
intercourse”, which might potentially aid in clarifying the
contribution of anxiety reduction, if present. It is possible as
well, that PE populations may differ in some neurophysi-
ological dimension, as compared to depressed or other clini-
cal populations for whom SSRIs are commonly prescribed.
However, post SSRI persistence of biological changes or
adaptations can by no means be ruled out [8], are supported
by animal studies [50-52], and thus ought to be a cause for
Brief courses of twelve weeks, and of four weeks of
medication treatment in the Safarinejad and Hosseini [12]
and Arafa and Shamloul [13] studies were sufficient to result
in persistence of sexual side effects at very high rates in
healthy individuals not suffering from any psychiatric condi-
tion. The duration of SSRI treatment in these premature
ejaculation studies is considerably shorter than guidelines
recommend for approved conditions. It is not known whether
the sustained benefits remain stable over a longer period of
time than the six months assessed, however it is known that
medication-induced sexual side effects may change over the
course of time [53, 54]. Montejo and Majadas [53] note that
SSRI-related impotence may occur as secondary to disorders
of libido, orgasm, or ejaculation that have already lasted for
months. Further, they report a positive relationship between
the severity of difficulty maintaining sexual arousal and the
length of treatment. These findings, of persistent sexual
benefits after SSRI treatment discontinuation occurring at
high rates in healthy individuals, point to the need to assess
the post-treatment duration of the full range of SSRI and
SNRI sexual side effects, both positive and deleterious.
There seems little reason to assume that SSRI persistent sex-
ual side effects would be confined to those considered desir-
able by consumers and profitable to industry.
In a recent issue of Primary Psychiatry, the journal’s
editor [55], lamented the limits of the post-market pharma-
covigilance system, stating that “the time has come for more
innovative ways to capture the true incidence of drug safety
and tolerability profiles” [p.15]. He calls for careful attention
to any real-time, emerging, alternative database of unex-
pected adverse drug events. The Internet has proven to be a
powerful tool for providing just such a database.
Consumer-reported information regarding the persistence
of SSRI sexual side effects is available from the SSRIsex
Internet community []. Founded
in January of 2005, SSRIsex, a Yahoo discussion group, in-
cludes a diverse membership of over fifteen hundred* men
and women who report sexual dysfunctions that began as
side effects of SSRIs or SNRIs have persisted months and
years after stopping the medications. The group’s purpose is
mutual support, generation of hypotheses about what may
have led to the persistent sexual dysfunctions, sharing of
information about attempted solutions, and the hope of en-
gaging researchers and professionals in collaborative efforts
to understand and address the problem. The group member-
ships’ ongoing moderated conversation now includes over
twelve thousand postings. The site also includes a data base
where individuals may describe their case history, and nu-
merous voluntary polls related to specific side effects and
their duration, specific medications and how long they were
taken, as well as remedies attempted along with their results.
Although the group has not been systematically sur-
veyed, it appears on the basis of member postings and in-
formal poll information that any and all sexual side effects
that start on the medications may continue after stopping
them. Sexual side effects are reported also to sometimes
change over time: for example, there are indications that
what was initially experienced as a positive ejaculation delay
evolved over time into persistent post-medication low libido,
impotence, leaking semen, and a precipitous decline in qual-
ity of orgasm and genital sensation. Most characteristic of
48 The Open Psychology Journal, 2008, Volume 1 Audrey S. Bahrick
the condition is reduced genital sensitivity or genital anes-
thesia, reduced intensity of orgasm or ejaculatory anhedonia,
an absence of sexual thoughts or fantasies, erectile problems,
and a severely diminished or absent libido.
Information from those who were adolescents at the time
of beginning SSRIs/SNRIs indicates that adolescents are by
no means immune from sexual side effects, nor from long-
lasting post-medication effects. It appears that SSRIs and
SNRIs may derail the course of what appears to be on-track,
developmentally normative sexual functioning into the same
kinds of sexual side effects and persistent difficulties re-
ported by adults. Adolescents in the group seem particularly
daunted by the feeling of exclusion from full participation in
an important life domain, and the implications of the condi-
tion for quality of life, self-concept, intimacy, and future
partnership possibilities.
Member reports seem to concur that a shared persistent
effect of these medications is a profound diminishment of
the physical capacity to experience sexual pleasure. The day
to day conversation among this international group of ethni-
cally, gender, sexual orientation and age-diverse membership
suggests that the condition of living with post SSRI sexual
dysfunction is, for many, a more challenging problem than
the condition they originally sought to treat.
* accessed March 2008
Accumulating case reports of persistent post SSRI sexual
dysfunction have appeared in recent literature. All cases in-
volve healthy individuals with no sexual dysfunction re-
ported at baseline, where the treated condition remains in
remission, and SSRI or SNRI-emergent sexual dysfunctions
continue long after cessation of medication.
Csoka and Shipko [7] describe two men and one woman
with normal pre-medication sexual functioning who experi-
enced severely decreased libido, and reduced genital sensi-
tivity and/or reduced orgasmic sensation persisting for years
beyond SSRI or SNRI discontinuation. They suggest a num-
ber of biological hypotheses to account for the persistent side
effects, highlighting the possible role of medication-induced
changes in gene expression.
Csoka, Bahrick, and Mehtonen [8] report three more
similar cases. The cases of two men are characterized by
genital anesthesia, ejaculatory anhedonia, and extremely low
libido persisting for several years beyond SSRI or SNRI dis-
continuation. A third young man was treated at age 18 with
four months of fluoxetine for mild anxiety related to a phase
of life problem. The new-onset erectile dysfunction he expe-
rienced within days of beginning the SSRI has persisted un-
changed for eleven years. His libido remains intact. The
authors offer further discussion of the possible role of persis-
tent medication-induced epigenetic changes, and propose to
call the condition Post SSRI Sexual Dysfunction (PSSD).
Kauffman and Murdock [9] report the case of a 32-year
old women with no reported sexual problems at baseline,
treated for major depression with citalopram. Due to medica-
tion-emergent decreased libido, genital anesthesia, and or-
gasmic hypo-intensity, she chose to switch after one month
to nefazodone, which she continued for 14 months. They
report her reduced libido, reduced orgasmic intensity, and
genital anesthesia that began with citalopram continued un-
changed during nefazodone treatment, and has persisted for
the year following completion of all drug therapy. Lubrica-
tion and genital engorgement have remained intact.
Bolton, Sareen, and Reiss [6] report a case of genital an-
esthesia and ejaculatory anhedonia persisting six years be-
yond cessation of a course of sertraline in an otherwise
healthy young man with normal pre-morbid sexual function-
ing. The authors conclude that the young man’s symptoms
are more likely a result of a conversion disorder than a last-
ing medication effect. They base their inferences on the ab-
sence of similar reports in the literature and on the indica-
tions in the literature that genital anesthesia and ejaculatory
anhedonia are rare. The young man was offered an interpre-
tation related to sexual numbing as an unconscious wish to
protect himself from rejection, a rejection having been the
trigger for the long-resolved depressive symptoms. The pa-
tient maintained the conviction that his symptoms were a
result of his past medication use, and declined the offer of a
course of psychodynamic psychotherapy.
The post-market pharmacovigilance system, designed to
detect adverse drug events once medications are in wide-
spread use, depends heavily on industry initiative to collect,
evaluate, and report data from post marketing studies of their
own products [56], creating a major conflict of interest at the
heart of our science base. The assumption that sexual side
effects will resolve in all cases, the corollary lack of long
term follow-up, along with industry’s vested interest in out-
come make it improbable that the incidence and scope of the
problem of persistent SSRI/SNRI sexual side effects will be
forthcoming from industry-initiated studies.
Evidence of persistence of SSRI/SNRI sexual side effects
also seems unlikely to emerge via voluntary MedWatch re-
ports of health care providers, a system thought to capture
only a fraction of adverse drug events [57]. For reasons al-
ready discussed, patients as well as health professionals may
be skeptical that persistent sexual dysfunctions after medica-
tion discontinuation could be medication-related and may
misattribute post SSRI sexual dysfunction to psychological
causes. A mistaken belief held by many professionals that
one needs to be confident of the relationship of the drug to
the adverse event in order to report it, along with a common
misperception among both health professionals and the pub-
lic that most adverse drug events are already known at the
time of marketing [58], would seem to make the probability
especially low that the condition will be reported and identi-
fied by this system. While consumers are those directly af-
fected by adverse drug events and therefore have an incen-
tive to report, according to a recent Institute of Medicine
report [57] there currently exists no comprehensive method
for engaging consumers in the adverse drug event reporting
Individuals who have a positive therapeutic response to
an SSRI or SNRI, but who also develop sexual dysfunction,
are indeed presented with difficult choices in weighing the
benefits and risks of continued treatment, particularly when
Persistence of Sexual Dysfunction Side Effects The Open Psychology Journal, 2008, Volume 1 49
treatment is intended to be for the long term. By virtue of
their typically frequent and regular contact with clients, prac-
ticing psychologists, and especially the small number of pre-
scribing psychologists, are in a good position to appreciate
and be responsive to the impact of SSRI/SNRI treatment on
sexual functioning within the full context of the client’s con-
dition and life circumstances [5]. Yet how are the appropri-
ate boundaries among treating professionals best defined?
When psychotherapy clients are under informed about medi-
cation side effects, who among the treatment providers is
responsible for informing clients of risks, and how do psy-
chologists and prescribing professionals most effectively
collaborate? How are client welfare and the treatment alli-
ance with the prescribing professional best protected, and
under what circumstances would psychologists risk raising
client anxiety about the recommendations of their medica-
tion-prescribing professional? The reviewed information
suggests that for individuals who develop SSRI or SNRI-
related sexual dysfunction, there exists an unknown prob-
ability that the dysfunctions will continue after medication
cessation. Under what circumstances should clients be in-
formed of that risk and by whom?
Psychologists are not negligent as professionals when
turning to the formal literature to inform themselves. How-
ever when the formal knowledge base is inadequate or inac-
curate, treatment providers are all left vulnerable to offering
hurtful interpretations or misleading information to clients in
spite of their best intentions and best efforts to become well-
informed. The inadequacies and inaccuracies in the knowl-
edge base have complex client-welfare and informed consent
implications. Informed consent includes an accurate acknow-
ledgement of limits of knowledge. Those limits impose more
serious risks than have been realized given the possibility of
medication-induced sexual dysfunctions persisting after
treatment. Compounding these risks is the near impossibility
of gaining a clear picture of how these medications may af-
fect adolescents and children who have no well-established
sexual functioning baseline or who are undeveloped sexu-
It is important that research go forward to fill in the gaps
in knowledge and that information become available through
means that prescribing health professionals find credible.
Psychologists should take an active role in this process, seek-
ing to integrate qualitative information from client-reported
experiences into the formal knowledge base, and producing
original outcome research independent of industry funding
and influence.
Absent peer-reviewed research, the convergent informa-
tion presented here, derived from case reports, incidental
research findings, evidence of the persistence of SSRI effects
on ejaculation latency, and the experiences of the SSRIsex
Internet community membership, currently represents the
best available source of information about an SSRI/SNRI-
related risk that is of public health significance. The SSRIsex
Internet community in particular has credibly gathered, pre-
sented and communicated qualitative experiences not cap-
tured in the research and not included in the drug’s labeling.
While each individual report among the Internet group
membership is anecdotal, the weight and substance of this
collective narrative urgently needs to be reconciled and inte-
grated into the existing knowledge base.
I wish to express my appreciation to Mark Harris for his
thoughtful reading of and comments on an earlier version of
this manuscript, to Julie Corkery for engaging discussions
that helped me to clarify a number of ideas presented, and to
Beth Rom-Rymer, Sam Cochran, David Antonuccio and
Kevin Bennett for their encouragement of my work. I also
want to thank Antonei Csoka for bringing the alternative
interpretation of the Montejo et al. [11] outcome data to my
Portions of the content of this manuscript were presented
at the 2007 American Psychological Association (APA)
Convention in San Francisco, as part of a symposium orga-
nized by APA Division 55 (Pharmacotherapy).
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Received: December 18, 2007 Revised: March 24, 2008 Accepted: April 22, 2008
© Audrey S. Bahrick; Licensee Bentham Open.
This is an open access article distributed under the terms of the Creative Commons Attribution License (, which
permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.
... Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drug which is prescribed for the treatment of a variety of disorders, including major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, generalized anxiety disorder, and impulse control disorders. 32 Among antidepressant agents, due to comparable efficacy, simple titration manner, better tolerability and greater safety profile in the event of overdose use, they have substituted the older generation of antidepressant drugs. 33,34 The following data can shed light on its use in a wide range: It has been reported that one in eight people have utilized one of the SSRIs in the past 10 years. ...
... 35 However, the exact prevalence of this type of persistent sexual dysfunction after discontinuation of SSRIs has not been well known. 32 Post-SSRI sexual dysfunction also can occur after only one dose of the drug. 33 Management of SSRI-induced sexual dysfunction seems to be complex and hard. ...
Full-text available
Any type of sexual dysfunction is an important problem in half of the patients with depressive disorder. On the other hand, one to a quarter of people without any depressive disorder experience sexual dysfunction. Antidepressant agents can lead to all types of sexual side effects including arousal, libido, orgasm and ejaculation problems. Selective serotonin reuptake inhibitors (SSRIs) are a widely used class of drugs which are prescribed for the treatment of a variety of disorders, including major depressive disorder, obsessive-compulsive disorder, posttraumatic stress disorder, panic disorder, generalized anxiety disorder, and impulse control disorders. It has been reported that one in eight people have utilized one of the SSRIs in the past 10 years. Some studies reported up to 80% of SSRI-induced sexual side effects. Management of SSRI-induced sexual dysfunction seems to be complex and hard. In this paper, SSRI-induced sexual dysfunction and new perspectives in the management of this problem were reviewed.
... 14,15 Further, the prescription of SSRI and SNRI medications may lead to loss of sexual desire for some patients even after treatment. 16 As for loss of appetite, the appetite hormones are sensitive to acute and chronic stress, and thus, appetite may be increased or decreased in patients with anxiety. 17 Although patients with unipolar depression more frequently suffer from inappetence and insomnia than bipolar patients, patients with bipolar disorder tend to report inappetence and insomnia together. ...
... Antidepressant drugs are among the most prescribed drugs worldwide because of their high reliability and low side effect profiles in the treatment. Selective serotonin reuptake inhibitors (SSRIs) can be used in the treatment of many psychiatric disorders such as major depressive disorder, generalized anxiety disorder, panic disorder (Bahrick & Audrey 2008). At the same time, it is frequently prescribed in cases of dermatological diseases such as atopic dermatitis, psoriasis, alopecia areata accompanied by psychiatric diseases or psychiatric symptoms (Gupta & Gupta 1996). ...
... The drugs used to regulate serotonin levels such as serotonin reuptake inhibitors may also cause serotonin toxicity (i.e., serotonin syndrome) due to their irreversible characteristics. Similarly, non-selective and irreversible MAO inhibitors can lead to the cheese effect, hypertension, etc. Dizziness, sexual dysfunction, dry mouth, emotional blunting and weight gain [25][26][27] are some other side effects associated with these traditional antidepressant drugs. The primary symptoms are such as confusion, agitation, restlessness and insomnia may be induced with the excess of serotonin [28,29]. ...
According to the World Health Organization (WHO), depression is a common mental disorder and includes complex interaction between social and psychological behaviour affecting 264 million people worldwide. The review aims to highlight the role and importance of nitrogen-based heterocyclics in the development of antidepressant compounds. Many research groups have attempted to design drug candidates capable of binding within the receptors. The commonest drug design strategy includes the incorporation of different structural features widely recognized as an antidepressant in the synthesized derivatives to enhance their CNS antidepressant effects. In this review, we have shed light on nitrogenous heterocyclic moieties such as quinazoline, pyridine, pyrimidine, pyrrolidine, imidazole, pyrazole, piperidine, oxadiazole, benzimidazole, benzothiazole, piperazine, triazine, purine, benzoxazole, and isoxazole as core nucleus and/or in combination as an antidepressant compound. These molecules with different structural features were noted to exert their antidepressant effects by multiple mechanisms viz., selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase (MAO) inhibitors, and Catechol-O-methyltransferase (COMT) inhibitors. The review focuses on the selection of these heterocyclic moieties for the further design and development of promising antidepressants by taking a clue from the earlier reported potent antidepressant compounds or from the marketed products. The results have been correlated with their structural activity relationship (SAR) to identify the substituents for the potency and selectivity within the receptors. This review might help the researchers working in the antidepressant field to develop more novel molecules that could fill the gap by improving potency and reducing toxicity.
... A review article published by Bahrick in the same year highlighted the signifi cance of two large placebo controlled studies into the use of SSRIs as a treatment for premature ejaculation [16]. The studies by Safarinejad and Hosseini [17], and by Arafa and Shamloul [18], found that the ejaculation-delaying effects of citalopram and sertraline, respectively, persisted for a signifi cant number of participants at 3and 6-month follow-up after the drugs had been withdrawn. ...
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Article as a citizen petition that leads the EMA (June 2019) to advice the risk of post-SSRI sexual dysfunction in the antidepressants prospect
Selective serotonin reuptake inhibitors (SSRI) show high efficacy in treating depression, however during treatment side effects, like for instance sexual dysfunction, may appear, decreasing compliance. In some cases, this condition will last after drug discontinuation, leading to the so-called post-SSRI sexual dysfunction (PSSD). The etiology of PSSD is still unknown, however a role for neuroactive steroids may be hypothesized. Indeed, these molecules are key physiological regulators of the nervous system, and their alteration has been associated with several neuropathological conditions, including depression. Additionally, neuroactive steroids are also involved in the control of sexual function. Interestingly, sexual dysfunction induced by SSRI treatment has been also observed in animal models. On this basis, we have here evaluated whether a subchronic treatment with paroxetine for two weeks and/or its withdrawal (i.e., a month) may affect the levels of neuroactive steroids in brain areas (i.e., hippocampus, hypothalamus, and cerebral cortex) and/or in plasma and cerebrospinal fluid of male rats. Data obtained indicate that the SSRI treatment alters neuroactive steroid levels and the expression of key enzymes of the steroidogenesis in a brain tissue- and time-dependent manner. Indeed, these observations with the finding that plasma levels of neuroactive steroids are not affected suggest that the effect of paroxetine treatment is directly on neurosteroidogenesis. In particular, a negative impact on the expression of steroidogenic enzymes was observed at the withdrawal. Therefore, it is possible to hypothesize that altered neurosteroidogenesis may also occur in PSSD and consequently it may represent a possible pharmacological target for this disorder.
This article casts a critical eye over the development of American psychiatry from 1980 to the present. It notes the rapid decline of psychoanalysis that followed the publication of DSM III; the rising influence of genetics and neuroscience; the re-emphasis on the biology of mental illness; and the collapse of public psychiatry that accompanied deinstitutionalization. It argues that while genetics and neuroscience have made scientific progress, the clinical utility of their findings to date has been very limited. The fifth edition of the DSM was supposed to base itself on this new science but that proved impossible. Diagnosis remains purely phenomenological and controversial. One of the ironies of research on psychiatric genetics is that has failed to find either a Mendelian origin of schizophrenia and depression or to validate the importance of hypothesized candidate genes. Genome-wide association studies have instead uncovered risk factors for major mental illnesses, but these overlap considerably, and the genetic associations are not dispositive. Most of those who carry these genetic variants do not develop mental illness. The status of psychopharmacology since the mid-1950s is scrutinized, as is the influence of the pharmaceutical industry on contemporary psychiatry, and the implications of its recent decision to abandon work in this arena. The paper concludes with an assessment of the crisis that it contends confronts contemporary American psychiatry: its overemphasis on biology; the urgent questions that persist about diagnosis and therapeutics; concerns about the directions of future research; and its inability to reduce the excess mortality that plagues the mentally ill.
Background: Post-SSRI Sexual Dysfunction (PSSD) is characterized by sexual and emotional symptoms associated to the exposure to Selective Serotonin Reuptake Inhibitors (SSRI) or Serotonin Noradrenaline Reuptake Inhibitors (SNRI). Objective: The present study provides a comprehensive picture on demographic and clinical characteristics associated to PSSD. Methods: An online survey was run on subjects self-declaring as affected by PSSD. The survey collected socio-demographic and clinical data via questions created ad hoc and three standardized scales (Arizona Sexual Experiences Scale, Hospital Anxiety and Depression Scale, World Health Organization Wellbeing Index). Results: A total of 135 subjects (115 males; mean age 31.9 ± 8.9 years) was analysed. The syndrome was more represented among young, heterosexual males after the exposure to SSRI/SNRI at relatively high doses. The major findings involved the temporal sequence of symptoms: 118 subjects had symptoms both during and after SSRI/SNRI administration, and 17 only after, thus deposing for a iatrogenic action of SSRI/SNRI. Different variables, represented by both emotional and sexual symptoms, accounted for the variability of the severity of the sexual dysfunction as well as of wellbeing. Conclusions: Based on the present results, PSSD is a complex iatrogenic syndrome in need of being further studied and understood.
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SSRI therapy is commonly associated with sexual side effects, but it is assumed that these distressing symp-toms resolve with termination of therapy. The atypical antidepressant nefazodone is infrequently associated with sexual dysfunction and may be substituted for SSRI's when sexual symptoms are intolerable. Recently, scattered case reports of persistent sexual dysfunction and genital anesthesia persisting well after termination of SSRI antidepressant therapy have surfaced. In each case, the underlying depressive disorder was in remission. Case: A 32-year old women with major depression was treated with citalopram but switched to nefazodone after 4 weeks of therapy due to genital anesthesia and orgasmic dysfunction. These symptoms continued following institution of nefa-zodone therapy and have persisted for over a year since termination of antidepressant treatment. Her depression remains in full remission. Discussion: It is likely that persistent post-treatment genital anesthesia and other sexual side effects are underreported, and physicians should be aware of this bothersome phenomenon. Formal post-treatment surveillance for this condition is war-ranted. Pharmacogenomic research may ultimately allow physicians to predict who is at risk for antidepressant induced sexual side effects.
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To determine the prevalence of and factors associated with the off-label use of antidepressant, anticonvulsant, and antipsychotic medications. A retrospective analysis of Georgia Medicaid recipients was conducted. Recipients prescribed antidepressant, anticonvulsant, or antipsychotic medications were identified. Logistic regression analysis was used to identify factors associated with off-label use. A total of 46,976 (75.42%) antidepressant recipients, 38,497 (80.12%) anticonvulsant recipients, and 21,252 (63.62%) antipsychotic recipients received at least 1 of these medications off-label in 2001. The likelihood of receiving off-label medications increased remarkably with advancing age (>or= 65 vs. < 65 years: antidepressant: OR = 5.15, 95% CI = 4.76 to 5.56; anticonvulsant: OR = 4.54, 95% CI = 4.16 to 4.96; antipsychotic: OR = 5.21, 95% CI = 4.82 to 5.63). Although receiving new anticonvulsants launched after 1993 was the strongest predictor (OR = 7.63, 95% CI = 7.07 to 8.23) of receiving off-label anticonvulsant medications, exposure to newer antidepressants and antipsychotics did not confer a higher chance of receiving off-label medications (selective serotonin reuptake inhibitors vs. tricyclic antidepressants: OR = 0.43, 95% CI = 0.40 to 0.45; atypical vs. conventional antipsychotics: OR = 0.76, 95% CI = 0.72 to 0.80). The off-label use of antidepressant, anticonvulsant, and antipsychotic medications is highly prevalent. Further research to study the effects of off-label use among this high risk subpopulation may be an important step toward defining the scope of and potential for such use.
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Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women. To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women. An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction. Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity. The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed. In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects. In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects. Identifier: NCT00375297.
How involved in the process of prescribing psychotropic drugs is the average practicing professional psychologist today? The answer is "far more than most people realize." Five hundred ninety-six practicing psychologists responded to a survey reporting the types of professional activities in which they regularly engage. Virtually all responding psychologists reported they were involved in making recommendations for medication evaluations, consulting with physicians about which medications to use with specific patients, and discussing medication-related issues with patients. A generally agreed-on model of psychopharmacology training for professional psychologists should emerge over the next 5 to 10 years.
Many psychologists are undecided on the appropriateness of obtaining prescriptive authority. The authors argue that, regardless of one's position or the outcome of this debate, all psychologists who provide or supervise clinical services must be knowledgeable about psychopharmacology. Lack of this knowledge will render psychologists ill prepared to adequately meet patient treatment needs. Whether psychologists work independently or in collaboration with primary care physicians, they need to have knowledge of the effects, side effects, and interactions of the many substances patients may be exposed to in order to help ensure that those patients are afforded the highest possible standard of care. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
One of the most important needs in clinical medicine is improved post-marketing surveillance of adverse drug reactions. Headlines in the popular press have recently highlighted an increasing number of drugs that have been in use for years that suddenly are withdrawn from the market or are tagged with a so-called "back-box warning" of a potentially life-threatening treatment-emergent event. Yet, there are numerous side effects of psychotropic drugs that are undesirable or that impact quality of life, that go unrecognized by prescribes. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
How involved in the process of prescribing psychotropic drugs is the average practicing professional psychologist today? The answer is "far more than most people realize." Five hundred ninety-six practicing psychologists responded to a survey reporting the types of professional activities in which they regularly engage. Virtually all responding psychologists reported they were involved in making recommendations for medication evaluations, consulting with physicians about which medications to use with specific patients, and discussing medication-related issues with patients. A generally agreed-on model of psychopharmacology training for professional psychologists should emerge over the next 5 to 10 years. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Psychologists rendering psychotherapeutic services to patients receiving pharmacological treatment with the newer antidepressants are becoming more familiar with their distinct therapeutic and side effect profiles. Increased attention has recently been directed at the sexual dysfunction associated with the use of these antidepressants. Among the newer agents, risk for the emergence of sexual side effects is greater with the selective serotonin reuptake inhibitors than with the atypical antidepressants. Psychologists who are aware of treatment-related sexual dysfunction may be more effective in collaborating with prescribing professionals to develop strategies that allow patients to minimize or better tolerate these side effects. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Selective Serotonin Reuptake Inhibitors (SSRIs) are designed to treat adults, but are increasingly prescribed for adolescents. SSRIs might cause permanent changes in serotonin-related behavior in adolescents, since their serotonergic system is still developing. Male Wistar rats were treated with paroxetine (15 mg/kg p.o.) or fluvoxamine (30 mg/kg p.o.) throughout adolescence. After a washout period their behavior in the elevated plusmaze, prepulse inhibition test, Forced swimming test and elevated T-maze were studied. In addition, the effects of the 5-HT1A receptor agonist 8-OH-DPAT on sexual behavior and lower lip retraction were measured. Paroxetine mildly inhibited weight gain during treatment. Both SSRIs caused a reduction in ejaculation frequency and in time spent on the open arm of the elevated plus-maze in adult rats. Fluvoxamine slightly increased avoidance latency in the elevated T-maze compared to paroxetine. No differences between the groups were found in the other tests. Apparently, chronic treatment with SSRIs during adolescence may cause mild changes in adult behavior.
Depression and antidepressant therapy have been associated with sexual dysfunction. Studies report wide discrepancies with regard to frequency, gender, and quality of sexual dysfunction. Although sexual side effects are a common reason for non-compliance with medication, information on impairment of sexuality in psychiatric patients is rare. The impact of antidepressant- induced sexual dysfunction is substantial and negatively affects quality of life, self-esteem, mood, and relationship with partner. Sexual side effects resulting from serotonin specific reuptake inhibitors use may be mediated by a number of central and peripheral mechanisms. Some antidepressants such as Bupropion, mirtazapine, and moclobemide have a sexual tolerability profile significantly better than SSRIs, especially escitalopram, paroxetine, venlafaxine, sertraline, or fluoxetine. There are some possibilities for treatment of anti-depressant induced sexual dysfunctions such as waiting for spontaneous remission, reducing the dosage level, substituting the offending drug with other antidepressants, drug holidays, or administration of a phosphodiesterase- 5-inhibitor. These side-effects are increasingly used therapeutically in the context of the common male sexual dysfunction ejaculatio praecox. For this indication short-acting SSRI;s are available.